Remnants of Cardinal Symptoms of Parkinson's Disease, Not Dyskinesia, Are Problematic for Dyskinetic Patients Performing Activities of Daily Living

Introduction: The impact of levodopa-induced dyskinesia (LID) on the daily lives of patients with Parkinson's disease (PD) remains to be determined. Furthermore, evidence suggests that cardinal motor symptoms of PD may coexist with LID, but their impact on activities of daily living (ADL) relative to LID is not known. This cross-sectional study aimed at determining the effect of LID and cardinal motor symptoms of PD on ADL in patients who were experiencing peak-dose choreic-type LID.Method: One hundred and twenty-one patients diagnosed with PD known to experience choreic-type LID were recruited for the study. Patients were asked to perform a set of ADL. Levels of LID, tremor, bradykinesia, and freezing of gait (FoG) were measured using 17 inertial sensors design to capture full body movements, while rigidity, and postural instability were assessed using clinical evaluations. Cognition was also assessed using the mini-mental state examination. Success criteria were set for each ADL using the time needed to perform the task and errors measured in 69 age-gender-matched healthy controls. Binary logistic regressions were used to identify symptoms influencing success or failure for each activity. Receiver operating characteristic curves were computed on each significant symptom, and Youden indexes were calculated to determine the critical level of symptomatology at which the performance significantly changed.Results: Results show that 97.7% of patients who presented with LID during the experiment also presented with at least one cardinal motor symptom. On average, patients took more time and did more errors during ADL. Multivariate analyses revealed that for the great majority of ADL, LID were not associated with worsening of performance; however, postural instability, tremor, rigidity, and cognitive decline significantly decreased the odds of success.Conclusions: Residual symptoms of PD, such as tremor, rigidity, and postural instability still present at peak-dose were more problematic than LID in the performance of ADL for patients experiencing slight-to-moderate LID. We also found that cognitive decline was associated with decreased performance in certain tasks. Therefore, a strategy using lower doses of medication to manage LID may be counterproductive since it would not address most of these symptoms already present in patients

Pacific food systems The role of fish and other aquatic foods for nutrition and health

This report is intended for actors, policymakers and funders concerned with improving food and nutrition security with fisheries as an entry point. It is equally valuable for food system, agricultural, health and nutrition actors who are seeking to protect and enhance the benefits that fish and other aquatic foods provide to a diversity of nutrition goals. This report has been developed from an extensive review of published scientific articles and technical reports, as well as interviews and consultations with 17 experts. It also draws upon insights from the Pacific Food System regional dialogues, which were held in the lead-up to the United Nations Food Systems Summit 2021

The Functions of Auxilin and Rab11 in Drosophila Suggest That the Fundamental Role of Ligand Endocytosis in Notch Signaling Cells Is Not Recycling

Notch signaling requires ligand internalization by the signal sending cells. Two endocytic proteins, epsin and auxilin, are essential for ligand internalization and signaling. Epsin promotes clathrin-coated vesicle formation, and auxilin uncoats clathrin from newly internalized vesicles. Two hypotheses have been advanced to explain the requirement for ligand endocytosis. One idea is that after ligand/receptor binding, ligand endocytosis leads to receptor activation by pulling on the receptor, which either exposes a cleavage site on the extracellular domain, or dissociates two receptor subunits. Alternatively, ligand internalization prior to receptor binding, followed by trafficking through an endosomal pathway and recycling to the plasma membrane may enable ligand activation. Activation could mean ligand modification or ligand transcytosis to a membrane environment conducive to signaling. A key piece of evidence supporting the recycling model is the requirement in signaling cells for Rab11, which encodes a GTPase critical for endosomal recycling. Here, we use Drosophila Rab11 and auxilin mutants to test the ligand recycling hypothesis. First, we find that Rab11 is dispensable for several Notch signaling events in the eye disc. Second, we find that Drosophila female germline cells, the one cell type known to signal without clathrin, also do not require auxilin to signal. Third, we find that much of the requirement for auxilin in Notch signaling was bypassed by overexpression of both clathrin heavy chain and epsin. Thus, the main role of auxilin in Notch signaling is not to produce uncoated ligand-containing vesicles, but to maintain the pool of free clathrin. Taken together, these results argue strongly that at least in some cell types, the primary function of Notch ligand endocytosis is not for ligand recycling

Auto detection and segmentation of daily living activities during a Timed Up and Go task in people with Parkinson’s disease using multiple inertial sensors

Abstract Background Wearable sensors have the potential to provide clinicians with access to motor performance of people with movement disorder as they undergo intervention. However, sensor data often have to be manually classified and segmented before they can be processed into clinical metrics. This process can be time consuming. We recently proposed detection and segmentation algorithms based on peak detection using Inertial Measurement Units (IMUs) to automatically identify and isolate common activities during daily living such as standing up, walking, turning, and sitting down. These algorithms were developed using a homogenous population of healthy older adults. The aim of this study was to investigate the transferability of these algorithms in people with Parkinson’s disease (PD). Methods A modified Timed Up And Go task was used since it is comprised of these activities, all performed in a continuous fashion. Twelve older adults diagnosed with early PD (Hoehn & Yahr ≤ 2) were recruited for the study and performed three trials of a 10 and 5-m TUG during OFF state. They were outfitted with 17 IMUs covering each body segment. Raw data from IMUs were detrended, normalized and filtered to reveal kinematics peaks that corresponded to different activities. Segmentation was accomplished by identifying the first minimum or maximum to the right and the left of these peaks. Segmentation times were compared to results from two examiners who visually segmented the activities. Specificity and sensitivity were used to evaluate the accuracy of the detection algorithms. Results Using the same IMUs and algorithms developed in the previous study, we were able to detect these activities with 97.6% sensitivity and 92.7% specificity (n = 432) in PD population. However, with modifications to the IMUs selection, we were able to detect these activities with 100% accuracy. Similarly, applying the same segmentation to PD population, we were able to isolate these activities within ~500 ms of the visual segmentation. Re-optimizing the filtering frequencies, we were able to reduce this difference to ~400 ms. Conclusions This study demonstrates the agility and transferability of using a system of IMUs to accurately detect and segment activities in daily living in people with movement disorders

Do Bradykinesia and Tremor Interfere in Voluntary Movement of Essential Tremor Patients? Preliminary Findings

Background:&nbsp;The aim of this study was to determine whether tremor and bradykinesia impacted a dexterous activity performed by patients with essential tremor (ET).Methods:&nbsp;Core bradykinesia was assessed in 27 controls and 15 patients with ET using a rapid alternating movement (RAM) task. Then, participants performed a &ldquo;counting money&rdquo; counting tasks while equipped with inertial measurement units to detect and quantify tremor during movement. The time required to perform subsections of the tasks and the rate of failure (errors) were compared between groups using Mann&ndash;Whitney U tests and a chi-square test, respectively.Results:&nbsp;Patients with ET presented with significant bradykinesia during the RAM task and had more tremor during the counting money task. However, the time required to perform the task and rate of failure were similar between groups.Discussion:&nbsp;Results show that even though bradykinesia was detected during fast movements, and that tremor was present during a task requiring dexterity, both symptoms did not interfere with the performance of patients with ET. This pilot study suggests that there may be a threshold at which tremor will become problematic. Determining this threshold for a wide range of daily activities may help determine when it is appropriate to initiate treatment for patients with ET.</p

Liposomes Prevent \u3ci\u3ein vitro\u3c/i\u3e Hemolysis Induced by Streptolysin O and Lysenin

The need for alternatives to antibiotics in the fight against infectious diseases has inspired scientists to focus on antivirulence factors instead of the microorganisms themselves. In this respect, prior work indicates that tiny, enclosed bilayer lipid membranes (liposomes) have the potential to compete with cellular targets for toxin binding, hence preventing their biological attack and aiding with their clearance. The effectiveness of liposomes as decoy targets depends on their availability in the host and how rapidly they are cleared from the circulation. Although liposome PEGylation may improve their circulation time, little is known about how such a modification influences their interactions with antivirulence factors. To fill this gap in knowledge, we investigated regular and long-circulating liposomes for their ability to prevent in vitro red blood cell hemolysis induced by two potent lytic toxins, lysenin and streptolysin O. Our explorations indicate that both regular and long-circulating liposomes are capable of similarly preventing lysis induced by streptolysin O. In contrast, PEGylation reduced the effectiveness against lysenin-induced hemolysis and altered binding dynamics. These results suggest that toxin removal by long-circulating liposomes is feasible, yet dependent on the particular virulence factor under scrutiny

Remnants of Cardinal Symptoms of Parkinson's Disease, Not Dyskinesia, Are Problematic for Dyskinetic Patients Performing Activities of Daily Living

International audienc

Homestead pond polyculture can improve access to nutritious small fish

In Bangladesh, homestead pond aquaculture currently comprises a polyculture of large fish species but provides an ideal environment to integrate a range of small fish species. Small fish consumed whole, with bones, head and eyes, are rich in micronutrients and are an integral part of diets, particularly for the poor. Results from three large projects demonstrate that the small fish, mola (Amblypharyngodon mola) contributes significantly to the micronutrients produced from all fish, in homestead ponds, in one production cycle. Mola contributed 98%, 56% and 35% of the total vitamin A, iron and zinc produced, respectively, despite comprising only 15% of the total fish production by weight. If consumed within the household, mola could contribute half of the vitamin A and a quarter of the iron intake recommended for a family of four, annually. Homestead ponds are uniquely accessible to women who prepare the household food. Further dissemination of the carp-small fish technology provides opportunities to target women and men together for training on fish production and consumption, nutrition and gender equity. Women only training is also recommended to enable them to engage fully, without feeling dominated by men. Partnering with the fisheries and health sectors will encourage sustainable uptake of this promising technology. Clearly, dissemination could have significant health benefits; however, improved monitoring and evaluation, particularly of dietary diversity and diet quality are essential. Research priorities should also include the production techniques of other small indigenous fish species (SIS), besides mola, and the power dynamics between women and men in operating homestead ponds

Patient Portal Reminders for Pediatric Influenza Vaccinations: A Randomized Clinical Trial.

In a large health system, we evaluated the effectiveness of electronic health record patient portal reminders in increasing pediatric influenza vaccination rates. We conducted an intention-to-treat randomized clinical trial of 22 046 children from 6 months to &lt;18 years of age in 53 primary care practices. Patients (or parent and/or proxies) who were active portal users were randomly assigned to receive reminder messages framed as gains or losses or no messages. They were separately randomly assigned to receive a precommitment message before the influenza season. The primary outcome was receipt of ≥1 seasonal influenza vaccinations. Additionally, children 6 months to &lt;3 years of age due for a second influenza vaccine were randomly assigned to receive a reminder or no reminder for the second vaccination. First-dose influenza vaccination rates were 56.9% in the control group, 58.0% in the loss-frame reminders group (P = .07), and 58.0% in the gain-frame group (P = .47). Rates were 58.3% in the precommitment group versus 57.0% in the control group (P = .11). Adjusted risk ratios for first vaccination were 1.02 (95% confidence interval [CI]: 1.00-1.04) for loss-frame reminders, 1.01 (95% CI: 0.98-1.05) for gain-frame reminders, and 1.02 (95% CI: 1.00-1.04) for precommitment messages versus controls. Second-dose vaccination rates were 44.1% in the control group and 55.0% in the reminder group, with an adjusted risk ratio of 1.25 (95% CI: 1.07-1.45). Patient portal reminders for influenza vaccines in children, whether framed as gains or losses, did not increase first-dose influenza vaccination rates but were highly effective for the second dose of the vaccine